title: Galectin-9 is a suppressor of T and B cells and predicts the immune modulatory potential of mesenchymal stromal cell preparations.
abstract: Therapeutic approaches using multipotent mesenchymal stromal cells (MSCs) are advancing in regenerative medicine, transplantation, and autoimmune diseases. The mechanisms behind MSC immune modulation are still poorly understood and the prediction of the immune modulatory potential of single MSC preparations remains a major challenge for possible clinical applications. Here, we highlight galectin-9 (Gal-9) as a novel, important immune modulator expressed by MSCs, which is strongly upregulated upon activation of the cells by interferon-γ (IFN-γ). Further, we demonstrate that Gal-9 is a major mediator of the anti-proliferative and functional effects of MSCs not only on T cells but also on B cells. Here, Gal-9 and activated MSCs contribute to the suppression of antigen triggered immunoglobulin release. Moreover, we determined that Gal-9 expression could serve as a marker to predict a higher or lower immune modulatory potential of single cell preparations and therefore to distinguish the therapeutic potency of MSCs derived from different donors. Also in vivo co-administration of MSCs or murine Gal-9 resulted in significantly reduced IgG titers in mice immunized with human coagulation factor VIII (FVIII). In conclusion, Gal-9 acts as an immune modulator interfering with multiple cell types including B cells and Gal-9 may serve as a predictive indicator for clinical MSC therapy.
authors.affiliation: 1 Institute for Transfusion Medicine and Immune Hematology, Clinics of the Johann Wolfgang Goethe University , German Red Cross Blood Donor Service Baden-Wuerttemberg-Hessen, Frankfurt, Germany .
authors.forename: Christopher
authors.initials: C
authors.lastname: Ungerer
authors.forename: Patricia
authors.initials: P
authors.lastname: Quade-Lyssy
authors.forename: Heinfried H
authors.initials: HH
authors.lastname: Radeke
authors.forename: Reinhard
authors.initials: R
authors.lastname: Henschler
authors.forename: Christoph
authors.initials: C
authors.lastname: Königs
authors.forename: Ulrike
authors.initials: U
authors.lastname: Köhl
authors.forename: Erhard
authors.initials: E
authors.lastname: Seifried
authors.forename: Jörg
authors.initials: J
authors.lastname: Schüttrumpf
mesh_terms: D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005169:Factor VIII / Q000008:administration & dosage; D005260:Female; D037161:Galectins / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D056747:Immunomodulation / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D015415:Biomarkers; D037161:Galectins; D007074:Immunoglobulin G; C105032:LGALS9 protein, human; C508186:galectin 9, mouse; D007371:Interferon-gamma; C078147:F8 protein, human; D005169:Factor VIII